Recent Advances on the Function and Purification of Milk Exosomes: A Review

Abstract

Exosomes are nano-scale extracellular vesicles, which can be used as drug carriers, tumor treatment, intestinal development and immune regulator. That is why it has great potential in pharmacy, functional foods, nutritional supplements, especially those for infants, postoperative patients, chemotherapy patients and the elderly. In addition, abnormal exosome level is also related to diseases such as cardiovascular diseases, tumor, diabetes, neurodegenerative and autoimmune diseases, as well as infectious diseases. Despite its high biological significance, pharmaceutical and nutritional value, the low abundancy of exosomes in milk is one of the bottlenecks restricting its in-depth research and real-life application. At present, there is no unified standard for the extraction of breast milk exosomes. Therefore, choosing the proper extraction method is very critical for its subsequent research and development. Based on this, this paper reviewed the purification techniques, the function and the possible applications of milk exosomes based on 47 latest references. Humble advices on future directions, prospects on new ideas and methods which are useful for the study of exosomes are proposed at the end of the paper as well.

Advances in the protection of intestinal mucosal barrier function by milk-derived miRNAs

“…52 Four transmembrane proteins and membrane-bound proteins distributed on the surface of exosomes can effectively enhance the stability of miRNAs circulating in vivo . 9 Hata et al (2010) showed that compared to synthetic miRNAs and mRNAs, bovine milk miRNAs, and mRNAs could still show good stability under simulated gastric juice low pH environment and RNA enzyme conditions, and their utilization efficiency and quality were not affected. 53 Lopez Hazas et al (2022) similarly demonstrated that miRNAs encapsulated by bovine milk exosomes were more stable than free miRNAs and had better digestive tolerance, prolonging the degradation rate of specific miRNAs in mice.…”

“…As an intercellular communication molecule, milkderived exosomes can play an essential role in regulating signal transduction, immune tolerance, and inflammatory responses by delivering miRNAs they carry across borders to intestinal target cells through the food uptake pathway. [8][9][10] Accordingly, this paper summarizes and composes the research progress on the stability, transport mode, and uptake pattern of milk-derived miRNAs across species, focuses on the possible mechanisms of milk-derived miRNAs to protect the intestinal mucosal barrier, and also analyzes the effects of processing treatment on miRNAs in milk and dairy products to provide a reference for the development and utilization of milk-derived miRNAs in food. process of miRNAs in mammary cells has been initially elucidated.…”

Milk Exosomes from Gestational Diabetes Mellitus (GDM) and Healthy Parturient Exhibit Differential miRNAs Profiles and Distinct Regulatory Bioactivity on Hepatocyte Proliferation

“…Our results of fluorescent labeling experiment also confirm that HM exosomes can be uptake by cultured HepG2 cells, and also can be absorbed in the intestine of mice and distributed in mice liver, which is in agreement with previous reports. [ 1,37 ] Collectively, our results demonstrate that HM exosomes from GDM and healthy parturient exhibit distinct regulatory bioactivities on hepatocyte proliferation, which is probably because that GDM enriches miR‐101‐3p into HM exosomes, and HM exosomes from GDM parturient deliver miR‐101‐3p to target and downregulate mTOR in both cultured HepG2 cells and mice liver resulting in the inhibition of hepatocyte proliferation.…”

“…from mothers to breastfeeding infants. [1,7,16,36,37] Maternal health conditions influence the composition of HM exosomes and may further change the functionalities of HM exosomes. Results in this study and others [18] indicate that GDM changes the miRNA profiles in HM exo-somes.…”

Exosomes in Mastitis—Research Status, Opportunities, and Challenges

“…Several groups have compared the functional activity of bovine, buffalo, goat, and yak milk-derived exosomes [ 128 , 129 , 130 , 131 ]. As drug delivery vehicles, milk-derived exosomes present many advantages: safety as determined by failure to induce obvious immunogenicity or cytotoxicity [ 132 , 133 , 134 ]; ability to pass through barrier systems, such as the blood-brain barrier [ 135 ]; effective targeting [ 136 ], enhancement of the oral availability of drugs [ 137 ]; high stability against extreme stimuli [ 138 , 139 ]; standardization of cost and preparation processes [ 120 , 140 , 141 ], etc.…”